RESUMO
BACKGROUND & AIMS: The incidence of osteoporotic fractures is lower in countries in the Mediterranean basin. Virgin olive oil, a key component of the Mediterranean Diet (MDiet), with recognised beneficial effects on metabolism and cardiovascular health, may decrease the risk of osteoporotic fractures. The aim to this study was to explore the effect of chronic consumption of total olive oil and its varieties on the risk of osteoporosis-related fractures in a middle-aged and elderly Mediterranean population. METHODS: We included all participants (n = 870) recruited in the Reus (Spain) centre of the PREvención con DIeta MEDiterránea (PREDIMED) trial. Individuals, aged 55-80 years at high cardiovascular risk, were randomized to a MedDiet supplemented with extra-virgin olive oil, a MedDiet supplemented with nuts, or a low-fat diet. The present analysis was an observational cohort study nested in the trial. A validated food frequency questionnaire was used to assess dietary habits and olive oil consumption. Information on total osteoporotic fractures was obtained from a systematic review of medical records. The association between yearly repeated measurements of olive oil consumption and fracture risk was assessed by multivariate Cox proportional hazards. RESULTS: We documented 114 incident cases of osteoporosis-related fractures during a median follow-up of 8.9 years. Treatment allocation had no effect on fracture risk. Participants in the highest tertile of extra-virgin olive oil consumption had a 51% lower risk of fractures (HR:0.49; 95% CI:0.29-0.81. P for trend = 0.004) compared to those in the lowest tertile after adjusting for potential confounders. Total and common olive oil consumption was not associated with fracture risk. CONCLUSIONS: Higher consumption of extra-virgin olive oil is associated with a lower risk of osteoporosis-related fractures in middle-aged and elderly Mediterranean population at high cardiovascular risk.
Assuntos
Azeite de Oliva/uso terapêutico , Fraturas por Osteoporose , Idoso , Dieta Mediterrânea , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/dietoterapia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controleRESUMO
SAP18, a polypeptide associated with the Sin3-HDAC co-repressor complex, was identified in a yeast two-hybrid screen as capable of interacting with the Drosophila GAGA factor. The interaction was confirmed in vitro by glutathione S-transferase pull-down assays using recombinant proteins and crude SL2 nuclear extracts. The first 245 residues of GAGA, including the POZ domain, are necessary and sufficient to bind dSAP18. In polytene chromosomes, dSAP18 and GAGA co-localize at a few discrete sites and, in particular, at the bithorax complex where GAGA binds some silenced polycomb response elements. When the dSAP18 dose is reduced, flies heterozygous for the GAGA mutation Trl67 show the homeotic transformation of segment A6 into A5, indicating that GAGA-dSAP18 interaction contributes to the functional regulation of the iab-6 element of the bithorax complex. These results suggest that, through recruitment of the Sin3-HDAC complex, GAGA might contribute to the regulation of homeotic gene expression.
Assuntos
Proteínas de Transporte , Proteínas de Drosophila , Drosophila/embriologia , Histona Desacetilases/metabolismo , Proteínas de Homeodomínio/metabolismo , Fatores de Transcrição/metabolismo , Abdome/embriologia , Sequência de Aminoácidos , Animais , Proteínas Relacionadas à Autofagia , Sítios de Ligação , Coristoma/genética , Cromossomos/genética , Cromossomos/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Drosophila/genética , Drosophila/metabolismo , Proteínas de Homeodomínio/química , Proteínas de Homeodomínio/genética , Proteínas de Insetos/química , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Masculino , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase , Dados de Sequência Molecular , Mutação , Fenótipo , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas de Saccharomyces cerevisiae , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Complexo Correpressor Histona Desacetilase e Sin3 , Fatores de Transcrição/química , Fatores de Transcrição/genética , Técnicas do Sistema de Duplo-HíbridoRESUMO
The Drosophila GAGA factor self-oligomerizes both in vivo and in vitro. GAGA oligomerization depends on the presence of the N-terminal POZ domain and the formation of dimers, tetramers, and oligomers of high stoichiometry is observed in vitro. GAGA oligomers bind DNA with high affinity and specificity. As a consequence of its multimeric character, the interaction of GAGA with DNA fragments carrying several GAGA binding sites is multivalent and of higher affinity than its interaction with fragments containing single short sites. A single GAGA oligomer is capable of binding adjacent GAGA binding sites spaced by as many as 20 base pairs. GAGA oligomers are functionally active, being transcriptionally competent in vitro. GAGA-dependent transcription activation depends strongly on the number of GAGA binding sites present in the promoter. The POZ domain is not necessary for in vitro transcription but, in its absence, no synergism is observed on increasing the number of binding sites contained within the promoter. These results are discussed in view of the distribution of GAGA binding sites that, most frequently, form clusters of relatively short sites spaced by small variable distances.
